Effects of Sympathetic Denervation on Ventricular Function and Remodeling after Myocardial Infarction in Rats

• Grant number: 13/06130-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2014
• End date: January 31, 2016
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Luiz Felipe Pinho Moreira
• Grantee: Fernando Luiz Zanoni
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Cardiovascular diseases are the leading cause of death. Currently available pharmacological therapies and advances in interventional cardiology have increased the number of survival patients from acute cardiovascular events such as acute myocardial infarction (AMI). However, the heart failure that develops after injury to the myocardium has become the leading cause of morbidity and mortality. This is a chronic and progressive weakness of the myocardium, where ultrastructural and functional changes after myocardial ischemia will lead to ventricular remodeling. The pathological ventricular remodeling is influenced by a number of neuroendocrine factors such as the renin-angiotensin-aldosterone, catecholamines, oxidative stress, proinflammatory cytokines and endothelins. Sympathetic activation markedly influences ventricular remodeling, whereas pharmacological blockade of b-adrenergic receptors reduced or even reversed left ventricular remodeling in patients with heart failure and dilated left ventricle. Considering the potential benefit of sympathetic block on the development of cardiac remodeling after AMI this study aims to investigate the structural, inflammatory and functional changes in the myocardium of infarcted rats followed by sympathetic block by chemical sympathectomy. Male Wistar rats weighing 300 to 350 g will be anesthetized by a mixture of isoflurane and oxygen. Prior to surgical procedures the animals receive tramadol hydrochloride 10 mg / kg, ip, as analgesics. The AMI is induced by ligation of the ascending branch of left coronary artery and, 48 hours later, the animals will undergo chemical ablation of the stellate ganglion by injection of 100 microliters of absolute ethanol around the ganglion. The animals will be divided into four experimental groups: 1) Sham - rats underwent thoracotomy without induction of AMI and without sympathectomy, 2) AMI - infarcted rats, but not submitted to sympathectomy, 3) AMI + LS - infarcted rats underwent left sympathectomy; 4) AMI + BS - infarcted rats underwent bilateral sympathectomy. After 8 weeks of the initial procedures will be performed the following analysis: cardiac morphology, infarct size evaluation, cardiovascular function analysis by the pressure-volume curves; cytokines (IL-6 and IL-10), B-type natriuretic peptide and catecholamines (epinephrine and norepinephrine) levels will be determined by ELISA; quantification of gene expression of matrix metalloproteinases (MMP-1 and MMP-2) by real time RT-PCR; quantification MAP kinases p38, ERK1 and ERK2 by western blot; and expression of Bcl-2 and caspase-3 by immunohistochemistry.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZANONI, FERNANDO LUIZ; SIMAS, RAFAEL; DA SILVA, RAPHAEL GRILLO; BREITHAUPT-FALOPPA, ANA CRISTINA; COUTINHO E SILVA, RAPHAEL DOS SANTOS; JATENE, FABIO BISCEGLI; MOREIRA, LUIZ FELIPE P.. Bilateral sympathectomy improves postinfarction left ventricular remodeling and function. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, v. 153, n. 4, p. 855+, APR 2017. (13/06130-3)